Gut and Liver, Vol. 11, No. 5, September 2017, pp. 642-647
ORiginal Article
Comparison of the Outcomes of Peroral Endoscopic Myotomy for Achalasia According to Manometric Subtype Won Hee Kim1, Joo Young Cho1, Weon Jin Ko1, Sung Pyo Hong1, Ki Baik Hahm1, Jun-Hyung Cho2, Tae Hee Lee2, and Su Jin Hong3 1 Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, 2Digestive Disease Center, Soonchunhyang University Hospital, Seoul, and 3Digestive Disease Center, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
Background/Aims: We evaluated whether manometric subtype is associated with treatment outcome in patients with achalasia treated by peroral endoscopic myotomy (POEM). Methods: High-resolution manometry data and Eckardt scores were collected from 83 cases at two tertiary referral centers where POEM is performed. Manometric tracings were classified according to the three Chicago subtypes. Results: Among the 83 cases, 48 type I, 24 type II, and 11 type III achalasia cases were identified. No difference was found in pre-POEM Eckardt score, basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP) among the type I, type II, and type III groups. All three patient groups showed a significant improvement in postPOEM Eckardt score (6.1±2.1 to 1.5±1.5, p=0.001; 6.8±2.2 to 1.2±0.9, p=0.001; 6.6±2.0 to 1.6±1.4, p=0.011), LES pressure (26.1±13.8 to 15.4±6.8, p=0.018; 32.3±19.0 to 19.2±10.4, p=0.003; 36.8±19.2 to 17.5±9.7, p=0.041), and 4s IRP (21.5±11.7 to 12.0±8.7, p=0.007; 24.5±14.8 to 12.0±7.6, p=0.002; 24.0±15.7 to 11.8±7.1, p=0.019) at a median follow-up of 16 months. Conclusions: POEM resulted in a good clinical outcome for all manometric subtypes. (Gut Liver 2017;11:642-647) Key Words: Esophageal achalasia; Peroral endoscopic myotomy; High resolution manometry; Treatment outcome
INTRODUCTION Achalasia is an esophageal motility disorder of unknown cause. Achalasia is characterized by impaired relaxation of the lower esophageal sphincter (LES) and absent esophageal peristalsis, due to neuronal degeneration of the myenteric plexus. Estimated incidence is 1 per 100,000 per-year with a peak inci-
dence between the ages of 30 and 60 years.1 Available treatment options for achalasia are oral pharmacologic therapy, endoscopic injection of botulinum toxin, pneumatic dilatation, or laparoscopic myotomy. Of these, pneumatic dilatation and myotomy are considered the most effective treatment,2 with a favorable short-term outcome. However, the beneficial effect declines over time, and repeat intervention may be required.3 When compared with surgical myotomy, peroral endoscopic myotomy (POEM) is known to be a safe and effective form of endoscopic surgery for achalasia patients. Inoue and colleagues introduced POEM as an alternative treatment for achalasia patients in 2010.4,5 POEM has been performed worldwide in more than 7,000 cases, there is growing evidence that POEM can be a standard treatment for achalasia patients. Recent studies have reported excellent outcomes for POEM in terms of both symptom resolution and improvement in esophagogastric junction (EGJ) physiology and esophageal emptying. The treatment success rate of 89% to 100%4,6-9 have been reported for the treatment. Response to botulinum toxin injection or pneumatic dilatation was best in type II achalasia and somewhat lower in type I; patients with type III achalasia had a poor response to all forms of therapy, which is similar in laparoscopic Heller’s myotomy.9-11 However, the treatment outcomes for POEM, divided according to achalasia subtype as defined by high resolution manometry (HRM) have rarely been studied to the best of our knowledge. We therefore evaluated whether manometric subtype was associated with the treatment outcome in patients treated with POEM.
Correspondence to: Joo Young Cho Digestive Disease Center, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Korea Tel: +82-31-780-5641, Fax: +82-31-780-5219, E-mail: [email protected] Received on November 8, 2016. Revised on January 3, 2017. Accepted on January 3, 2017. Published online June 27, 2017 pISSN 1976-2283 eISSN 2005-1212 https://doi.org/10.5009/gnl16545
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Kim WH, et al: Peroral Endoscopic Myotomy for Achalasia
MATERIALS AND METHODS
(0, absent; 1, occasional; 2, daily; and 3, each meal) and weight loss (0, no weight loss; 1, 10 kg). Patients were followed postoperatively, every 3 months periods.
1. Patients This retrospective cohort study was conducted from November 2011 to December 2014 in two tertiary referral centers. This study was approved by the Institutional Review Board of Soonchunhyang University Hospital and CHA Bundang Medical Center, CHA University. Informed consent was obtained from all subjects. A total of 83 achalasia patients who underwent POEM were enrolled in our study. The diagnosis of achalasia was based on HRM. In addition, patients were required to have an Eckardt score of more than 3.12 The Eckardt score is the sum of the symptom scores for dysphagia, regurgitation, and chest pain
A
643
B
2. High resolution manometry The manometric data were collected pretreatment and at 12 months postoperatively. An HRM with 32 solid-state sensors spaced at 1 cm intervals (InSIGHTTMHRiM· system; Sandhill Scientific, Highlands Ranch, CO, USA) was used. Studies were performed with the patient in the sitting position after at least 6 hours of fasting. The manometric protocol included a 5-minute period to assess basal sphincter pressure and ten 5 mL-saline swallows.
C
Fig. 1. High-resolution manometry tracings of the three subtypes of achalasia. (A) Type I achalasia, (B) type II achalasia, and (C) type III achalasia.
A
B
C
D
E
F
Fig. 2. Peroral endoscopic myotomy (POEM) procedure. (A) Mucosal incision, (B) creation of a submucosal tunnel, (C) myotomy, (D, E) submucosal space difference between the esophageal and gastric side, and (F) closure.
644
Gut and Liver, Vol. 11, No. 5, September 2017
Manometric data were analyzed using the BioView software (Sandhill Scientific Inc.). Manometric tracings were classified according to the three Chicago subtypes:13 type I with impaired LES relaxation during swallow and aperistalsis of esophageal body, type II with pan-esophageal pressurization, type III with no normal peristalsis, but evidence of esophageal spasm (Fig. 1). The manometries were interpreted by experienced gastroenterologists (T.H.L. and W.H.K.). 3. POEM procedures POEM was performed under general anesthesia by expert endoscopists (J.Y.C. and S.J.H.). The procedure consisted of four consecutive steps: (1) mucosal incision: after 5 mL submucosal injection (mixture of sodium hyaluronate, normal saline, and indigo carmine), about 2 cm length vertical mucosal incision is made at 10 to 15 cm above the EGJ to allow entry into the submucosa; (2) creation of a submucosal tunnel: submucosal tunnel was made using spray coagulation until the LES was reached; (3) myotomy: dissection of the inner circular muscle bundle was started inside the submucosal tunnel, 2 cm distal to the mucosal entry site and more than 10 cm proximal to the EGJ. The myotomy should be extended 2 cm to the stomach cardia; and (4) closure: the mucosal entry was closed with multiple endoscopic clips (Fig. 2). 4. Outcomes measurements Eckardt score was recorded every 3 months periods. HRM and Endoscopy was performed 6 months and 12 months after POEM. The primary outcome was therapeutic success, defined by a reduction in the Eckardt score to ≤3. The secondary outcomes were LES pressure and integrated relaxation pressure (IRP) measured by HRM and other procedure related parameters. 5. Statistical analysis Statistical analysis was performed using SPSS 21.0 software (IBM Corp., Armonk, NY, USA). The mean values between baseline and follow-up were compared using Wilcoxon signed rank test for paired samples. Statistical significance between groups was evaluated using analysis of variance. A p-values of less than 0.05 was considered statistically significant.
RESULTS 1. Patient characteristics In total, 83 achalasia patients with a mean age of 45.2 years (range, 12 to 75 years) and 35 male patients (42.2%) were enrolled in the study. The mean duration of symptoms was 6.4 years, and 40 patients had received prior treatment for achalasia. Of them, 18 patients had 30 mm balloon dilatation, 12 had botulinum toxin injection, two had both balloon dilatation and botulinum toxin injection, two had laparoscopic Heller myotomy, and six had POEM (Table 1). In total, 48 patients had achalasia type I (57.8%), 24 patients had achalasia type II (28.9%), and 11 patients had achalasia type III (13.3%). There was no difference in the pre-POEM Eckardt score, basal LES pressure, and IRP between type I, type II, and type III groups (6.1±2.1 mm Hg vs 6.8±2.2 mm Hg vs 6.6±2.0 mm Hg, p=0.557; 26.1±13.8 mm Hg vs 32.3±19.0 mm Hg vs 36.8±19.2 mm Hg, p=0.137; 21.5±11.7 mm Hg vs 24.5±14.8 mm Hg vs 24.0±15.5 mm Hg, p=0.618). 2. Outcomes of POEM All of the POEMs were successfully performed without any serious complications. There was no significant difference in therapeutic success between the previously treated and treatment naive patients (97.4% vs 100%, p=0.433). Also, treatment success rate was similar in two independent endoscopists (67/69 [97.1%] vs 14/14 [100%], p=0.519) (Supplement Table 1). Capnoperitoneum occurred in 12.5% of patients, and was resolved with conservative treatment in all patients. Mucosal perforation was occurred in one patient. The mean procedure time of 83 patients was 91.1±35.8 minutes, mean length of the submucosal tunnel created was 12.2±3.3 cm, and the average length of myotomy was 9.0±2.8 cm. The procedure time, myotomy length, nil per os time, and hospital stay were no significantly different between the groups (Table 2). Treatment success, defined as an Eckardt score of
ORiginal Article
Comparison of the Outcomes of Peroral Endoscopic Myotomy for Achalasia According to Manometric Subtype Won Hee Kim1, Joo Young Cho1, Weon Jin Ko1, Sung Pyo Hong1, Ki Baik Hahm1, Jun-Hyung Cho2, Tae Hee Lee2, and Su Jin Hong3 1 Digestive Disease Center, CHA Bundang Medical Center, CHA University, Seongnam, 2Digestive Disease Center, Soonchunhyang University Hospital, Seoul, and 3Digestive Disease Center, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
Background/Aims: We evaluated whether manometric subtype is associated with treatment outcome in patients with achalasia treated by peroral endoscopic myotomy (POEM). Methods: High-resolution manometry data and Eckardt scores were collected from 83 cases at two tertiary referral centers where POEM is performed. Manometric tracings were classified according to the three Chicago subtypes. Results: Among the 83 cases, 48 type I, 24 type II, and 11 type III achalasia cases were identified. No difference was found in pre-POEM Eckardt score, basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP) among the type I, type II, and type III groups. All three patient groups showed a significant improvement in postPOEM Eckardt score (6.1±2.1 to 1.5±1.5, p=0.001; 6.8±2.2 to 1.2±0.9, p=0.001; 6.6±2.0 to 1.6±1.4, p=0.011), LES pressure (26.1±13.8 to 15.4±6.8, p=0.018; 32.3±19.0 to 19.2±10.4, p=0.003; 36.8±19.2 to 17.5±9.7, p=0.041), and 4s IRP (21.5±11.7 to 12.0±8.7, p=0.007; 24.5±14.8 to 12.0±7.6, p=0.002; 24.0±15.7 to 11.8±7.1, p=0.019) at a median follow-up of 16 months. Conclusions: POEM resulted in a good clinical outcome for all manometric subtypes. (Gut Liver 2017;11:642-647) Key Words: Esophageal achalasia; Peroral endoscopic myotomy; High resolution manometry; Treatment outcome
INTRODUCTION Achalasia is an esophageal motility disorder of unknown cause. Achalasia is characterized by impaired relaxation of the lower esophageal sphincter (LES) and absent esophageal peristalsis, due to neuronal degeneration of the myenteric plexus. Estimated incidence is 1 per 100,000 per-year with a peak inci-
dence between the ages of 30 and 60 years.1 Available treatment options for achalasia are oral pharmacologic therapy, endoscopic injection of botulinum toxin, pneumatic dilatation, or laparoscopic myotomy. Of these, pneumatic dilatation and myotomy are considered the most effective treatment,2 with a favorable short-term outcome. However, the beneficial effect declines over time, and repeat intervention may be required.3 When compared with surgical myotomy, peroral endoscopic myotomy (POEM) is known to be a safe and effective form of endoscopic surgery for achalasia patients. Inoue and colleagues introduced POEM as an alternative treatment for achalasia patients in 2010.4,5 POEM has been performed worldwide in more than 7,000 cases, there is growing evidence that POEM can be a standard treatment for achalasia patients. Recent studies have reported excellent outcomes for POEM in terms of both symptom resolution and improvement in esophagogastric junction (EGJ) physiology and esophageal emptying. The treatment success rate of 89% to 100%4,6-9 have been reported for the treatment. Response to botulinum toxin injection or pneumatic dilatation was best in type II achalasia and somewhat lower in type I; patients with type III achalasia had a poor response to all forms of therapy, which is similar in laparoscopic Heller’s myotomy.9-11 However, the treatment outcomes for POEM, divided according to achalasia subtype as defined by high resolution manometry (HRM) have rarely been studied to the best of our knowledge. We therefore evaluated whether manometric subtype was associated with the treatment outcome in patients treated with POEM.
Correspondence to: Joo Young Cho Digestive Disease Center, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Korea Tel: +82-31-780-5641, Fax: +82-31-780-5219, E-mail: [email protected] Received on November 8, 2016. Revised on January 3, 2017. Accepted on January 3, 2017. Published online June 27, 2017 pISSN 1976-2283 eISSN 2005-1212 https://doi.org/10.5009/gnl16545
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Kim WH, et al: Peroral Endoscopic Myotomy for Achalasia
MATERIALS AND METHODS
(0, absent; 1, occasional; 2, daily; and 3, each meal) and weight loss (0, no weight loss; 1, 10 kg). Patients were followed postoperatively, every 3 months periods.
1. Patients This retrospective cohort study was conducted from November 2011 to December 2014 in two tertiary referral centers. This study was approved by the Institutional Review Board of Soonchunhyang University Hospital and CHA Bundang Medical Center, CHA University. Informed consent was obtained from all subjects. A total of 83 achalasia patients who underwent POEM were enrolled in our study. The diagnosis of achalasia was based on HRM. In addition, patients were required to have an Eckardt score of more than 3.12 The Eckardt score is the sum of the symptom scores for dysphagia, regurgitation, and chest pain
A
643
B
2. High resolution manometry The manometric data were collected pretreatment and at 12 months postoperatively. An HRM with 32 solid-state sensors spaced at 1 cm intervals (InSIGHTTMHRiM· system; Sandhill Scientific, Highlands Ranch, CO, USA) was used. Studies were performed with the patient in the sitting position after at least 6 hours of fasting. The manometric protocol included a 5-minute period to assess basal sphincter pressure and ten 5 mL-saline swallows.
C
Fig. 1. High-resolution manometry tracings of the three subtypes of achalasia. (A) Type I achalasia, (B) type II achalasia, and (C) type III achalasia.
A
B
C
D
E
F
Fig. 2. Peroral endoscopic myotomy (POEM) procedure. (A) Mucosal incision, (B) creation of a submucosal tunnel, (C) myotomy, (D, E) submucosal space difference between the esophageal and gastric side, and (F) closure.
644
Gut and Liver, Vol. 11, No. 5, September 2017
Manometric data were analyzed using the BioView software (Sandhill Scientific Inc.). Manometric tracings were classified according to the three Chicago subtypes:13 type I with impaired LES relaxation during swallow and aperistalsis of esophageal body, type II with pan-esophageal pressurization, type III with no normal peristalsis, but evidence of esophageal spasm (Fig. 1). The manometries were interpreted by experienced gastroenterologists (T.H.L. and W.H.K.). 3. POEM procedures POEM was performed under general anesthesia by expert endoscopists (J.Y.C. and S.J.H.). The procedure consisted of four consecutive steps: (1) mucosal incision: after 5 mL submucosal injection (mixture of sodium hyaluronate, normal saline, and indigo carmine), about 2 cm length vertical mucosal incision is made at 10 to 15 cm above the EGJ to allow entry into the submucosa; (2) creation of a submucosal tunnel: submucosal tunnel was made using spray coagulation until the LES was reached; (3) myotomy: dissection of the inner circular muscle bundle was started inside the submucosal tunnel, 2 cm distal to the mucosal entry site and more than 10 cm proximal to the EGJ. The myotomy should be extended 2 cm to the stomach cardia; and (4) closure: the mucosal entry was closed with multiple endoscopic clips (Fig. 2). 4. Outcomes measurements Eckardt score was recorded every 3 months periods. HRM and Endoscopy was performed 6 months and 12 months after POEM. The primary outcome was therapeutic success, defined by a reduction in the Eckardt score to ≤3. The secondary outcomes were LES pressure and integrated relaxation pressure (IRP) measured by HRM and other procedure related parameters. 5. Statistical analysis Statistical analysis was performed using SPSS 21.0 software (IBM Corp., Armonk, NY, USA). The mean values between baseline and follow-up were compared using Wilcoxon signed rank test for paired samples. Statistical significance between groups was evaluated using analysis of variance. A p-values of less than 0.05 was considered statistically significant.
RESULTS 1. Patient characteristics In total, 83 achalasia patients with a mean age of 45.2 years (range, 12 to 75 years) and 35 male patients (42.2%) were enrolled in the study. The mean duration of symptoms was 6.4 years, and 40 patients had received prior treatment for achalasia. Of them, 18 patients had 30 mm balloon dilatation, 12 had botulinum toxin injection, two had both balloon dilatation and botulinum toxin injection, two had laparoscopic Heller myotomy, and six had POEM (Table 1). In total, 48 patients had achalasia type I (57.8%), 24 patients had achalasia type II (28.9%), and 11 patients had achalasia type III (13.3%). There was no difference in the pre-POEM Eckardt score, basal LES pressure, and IRP between type I, type II, and type III groups (6.1±2.1 mm Hg vs 6.8±2.2 mm Hg vs 6.6±2.0 mm Hg, p=0.557; 26.1±13.8 mm Hg vs 32.3±19.0 mm Hg vs 36.8±19.2 mm Hg, p=0.137; 21.5±11.7 mm Hg vs 24.5±14.8 mm Hg vs 24.0±15.5 mm Hg, p=0.618). 2. Outcomes of POEM All of the POEMs were successfully performed without any serious complications. There was no significant difference in therapeutic success between the previously treated and treatment naive patients (97.4% vs 100%, p=0.433). Also, treatment success rate was similar in two independent endoscopists (67/69 [97.1%] vs 14/14 [100%], p=0.519) (Supplement Table 1). Capnoperitoneum occurred in 12.5% of patients, and was resolved with conservative treatment in all patients. Mucosal perforation was occurred in one patient. The mean procedure time of 83 patients was 91.1±35.8 minutes, mean length of the submucosal tunnel created was 12.2±3.3 cm, and the average length of myotomy was 9.0±2.8 cm. The procedure time, myotomy length, nil per os time, and hospital stay were no significantly different between the groups (Table 2). Treatment success, defined as an Eckardt score of
